Genome-Wide Lymphocytic mRNA Sequencing to Identify Epithelial-Mesenchymal Transition Mechanism in Silicosis

Abstract Background Lymphocytes are immune cells that play dual roles in the pathogenesis of silicosis. Epithelial-mesenchymal transition (EMT), a vital phenomenon in the pathogenesis of silicosis, is regulated by cytokines, chemokines, and other molecules secreted by lymphocytes; however, the underlying regulatory mechanism is unclear. Here, we investigated the role of lymphocytes in EMT in silicosis. Methods Three patients with silicosis and three healthy controls that underwent pre-job physical examination were recruited; fasting venous blood samples were collected and lymphocytes were separated by Ficoll. High-throughput sequencing technology and bioinformatic analysis were used to identify specific genes and signaling pathways. The results were verified through the detection of related indices of peripheral blood samples. Results The baseline characteristics of subjects from silicosis group were matched with those of healthy controls. In comparison with healthy controls, patients with silicosis showed 1915 dysregulated genes that were thought to participate in various biological processes, including angiogenesis, tissue repair, cell proliferation, invasion, migration, and EMT. Protein-protein interaction analysis grouped these genes into three hub targets, including phosphoinositide 3-kinase (PI3K), integrin beta 1 (ITGB1), and integrin-linked protein kinase (ILK). Gene set enrichment analysis (GSEA) confirmed that PI3K, ITGB1, and ILK were tightly associated with EMT through the Wnt signaling pathway, Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway, and cell adhesion molecular pathway. ITGB1 is a member of the adhesion molecule family. The identified genes were verified through the detection of soluble adhesion molecules in peripheral blood samples of patients with silicosis and healthy subjects. Conclusion Dysregulation of PI3K, ITGB1, and ILK in lymphocytes may contribute to EMT via JAK-STAT, Wnt, and cell adhesion molecular pathways in patients with silicosis.